Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions
Identifieur interne : 004039 ( Main/Exploration ); précédent : 004038; suivant : 004040Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions
Auteurs : Valentin Goede [Allemagne] ; Kirsten Fischer [Allemagne] ; Raymonde Busch [Allemagne] ; Anja Engelke [Allemagne] ; Barbara Eichhorst [Allemagne] ; Clemens M. Wendtner [Allemagne] ; Tatiana Chagorova [Russie] ; Javier De La Serna [Espagne] ; Marie-Sarah Dilhuydy [France] ; Thomas Illmer ; Stephen Opat [Australie] ; Carolyn J. Owen [Canada] ; Olga Samoylova [Russie] ; Karl-Anton Kreuzer [Allemagne] ; Stephan Stilgenbauer [Allemagne] ; Hartmut Döhner [Allemagne] ; Anton W. Langerak [Pays-Bas] ; Matthias Ritgen [Allemagne] ; Michael Kneba [Allemagne] ; Elina Asikanius [Suisse] ; Kathryn Humphrey [Royaume-Uni] ; Michael Wenger [États-Unis] ; Michael Hallek [Allemagne]Source :
- The New England journal of medicine [ 0028-4793 ] ; 2014.
Descripteurs français
- Pascal (Inist)
- Wicri :
English descriptors
- KwdEn :
Abstract
BACKGROUND The monoclonal anti-CD20 antibody rituximab, combined with chemotherapeutic agents, has been shown to prolong overall survival in physically fit patients with previously untreated chronic lymphocytic leukemia (CLL) but not in those with coexisting conditions. We investigated the benefit of the type 2, glycoengineered antibody obinutuzumab (also known as GA101) as compared with that of rituximab, each combined with chlorambucil, in patients with previously untreated CLL and coexisting conditions. METHODS We randomly assigned 781 patients with previously untreated CLL and a score higher than 6 on the Cumulative Illness Rating Scale (CIRS) (range, 0 to 56, with higher scores indicating worse health status) or an estimated creatinine clearance of 30 to 69 ml per minute to receive chlorambucil, obinutuzumab plus chlorambucil, or rituximab plus chlorambucil. The primary end point was investigator-assessed progression-free survival. RESULTS The patients had a median age of 73 years, creatinine clearance of 62 ml per minute, and CIRS score of 8 at baseline. Treatment with obinutuzumab-chlorambucil or rituximab-chlorambucil, as compared with chlorambucil monotherapy, increased response rates and prolonged progression-free survival (median progression-free survival, 26.7 months with obinutuzumab-chlorambucil vs. 11.1 months with chlorambucil alone; hazard ratio for progression or death, 0.18; 95% confidence interval [CI], 0.13 to 0.24; P<0.001; and 16.3 months with rituximab-chlorambucil vs. 11.1 months with chlorambucil alone; hazard ratio, 0.44; 95% CI, 0.34 to 0.57; P<0.001). Treatment with obinutuzumab-chlorambucil, as compared with chlorambucil alone, prolonged overall survival (hazard ratio for death, 0.41; 95% CI, 0.23 to 0.74; P=0.002). Treatment with obinutuzumab-chlorambucil, as compared with rituximab-chlorambucil, resulted in prolongation of progression-free survival (hazard ratio, 0.39; 95% CI, 0.31 to 0.49; P<0.001) and higher rates of complete response (20.7% vs. 7.0%) and molecular response. Infusion-related reactions and neutropenia were more common with obinutuzumab-chlorambucil than with rituximab-chlorambucil, but the risk of infection was not increased. CONCLUSIONS Combining an anti-CD20 antibody with chemotherapy improved outcomes in patients with CLL and coexisting conditions. In this patient population, obinutuzumab was superior to rituximab when each was combined with chlorambucil.
Affiliations:
- Allemagne, Australie, Canada, Espagne, France, Pays-Bas, Royaume-Uni, Russie, Suisse, États-Unis
- Alberta, Bade-Wurtemberg, Bavière, Communauté de Madrid, District de Haute-Bavière, District de Tübingen, Hollande-Méridionale, Schleswig-Holstein
- Calgary, Kiel, Madrid, Munich, Rotterdam, Ulm
- Université de Calgary
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Wendtner</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>German CLL Study Group, Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne</s1><s2>Cologne</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>14 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>University Hospital Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Klinikum Schwabing</s1><s2>Munich</s2><s3>DEU</s3><sZ>6 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName></affiliation></author><author><name sortKey="Chagorova, Tatiana" sort="Chagorova, Tatiana" uniqKey="Chagorova T" first="Tatiana" last="Chagorova">Tatiana Chagorova</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Penza Regional Oncology Dispensary</s1><s2>Penza</s2><s3>RUS</s3><sZ>7 aut.</sZ></inist:fA14><country>Russie</country><wicri:noRegion>Penza Regional Oncology Dispensary</wicri:noRegion></affiliation></author><author><name sortKey="De La Serna, Javier" sort="De La Serna, Javier" uniqKey="De La Serna J" first="Javier" last="De La Serna">Javier De La Serna</name><affiliation wicri:level="3"><inist:fA14 i1="10"><s1>Servicio De Hematologia, Hospital Universitario 12 De Octubre</s1><s2>Madrid</s2><s3>ESP</s3><sZ>8 aut.</sZ></inist:fA14><country>Espagne</country><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName></affiliation></author><author><name sortKey="Dilhuydy, Marie Sarah" sort="Dilhuydy, Marie Sarah" uniqKey="Dilhuydy M" first="Marie-Sarah" last="Dilhuydy">Marie-Sarah Dilhuydy</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Hôpital Haut Lévêque</s1><s2>Bordeaux, Pessac</s2><s3>FRA</s3><sZ>9 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>Pessac</wicri:noRegion><wicri:noRegion>Hôpital Haut Lévêque</wicri:noRegion><wicri:noRegion>Hôpital Haut Lévêque</wicri:noRegion></affiliation></author><author><name sortKey="Illmer, Thomas" sort="Illmer, Thomas" uniqKey="Illmer T" first="Thomas" last="Illmer">Thomas Illmer</name></author><author><name sortKey="Opat, Stephen" sort="Opat, Stephen" uniqKey="Opat S" first="Stephen" last="Opat">Stephen Opat</name><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Department of Haematology, Monash Medical Centre</s1><s2>Clayton</s2><s3>AUS</s3><sZ>11 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Clayton</wicri:noRegion></affiliation></author><author><name sortKey="Owen, Carolyn J" sort="Owen, Carolyn J" uniqKey="Owen C" first="Carolyn J." last="Owen">Carolyn J. Owen</name><affiliation wicri:level="4"><inist:fA14 i1="13"><s1>University of Calgary</s1><s2>Calgary, AB</s2><s3>CAN</s3><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Calgary</settlement><region type="state">Alberta</region></placeName><orgName type="university">Université de Calgary</orgName></affiliation></author><author><name sortKey="Samoylova, Olga" sort="Samoylova, Olga" uniqKey="Samoylova O" first="Olga" last="Samoylova">Olga Samoylova</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Regional Clinical Hospital N.A. Semashko</s1><s2>Nizhny Novgorod</s2><s3>RUS</s3><sZ>13 aut.</sZ></inist:fA14><country>Russie</country><wicri:noRegion>Regional Clinical Hospital N.A. Semashko</wicri:noRegion></affiliation></author><author><name sortKey="Kreuzer, Karl Anton" sort="Kreuzer, Karl Anton" uniqKey="Kreuzer K" first="Karl-Anton" last="Kreuzer">Karl-Anton Kreuzer</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>German CLL Study Group, Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne</s1><s2>Cologne</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>14 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>University Hospital Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation></author><author><name sortKey="Stilgenbauer, Stephan" sort="Stilgenbauer, Stephan" uniqKey="Stilgenbauer S" first="Stephan" last="Stilgenbauer">Stephan Stilgenbauer</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Department of Internal Medicine III, Ulm University</s1><s2>Ulm</s2><s3>DEU</s3><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Ulm</settlement></placeName></affiliation></author><author><name sortKey="Dohner, Hartmut" sort="Dohner, Hartmut" uniqKey="Dohner H" first="Hartmut" last="Döhner">Hartmut Döhner</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Department of Internal Medicine III, Ulm University</s1><s2>Ulm</s2><s3>DEU</s3><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Ulm</settlement></placeName></affiliation></author><author><name sortKey="Langerak, Anton W" sort="Langerak, Anton W" uniqKey="Langerak A" first="Anton W." last="Langerak">Anton W. Langerak</name><affiliation wicri:level="3"><inist:fA14 i1="14"><s1>Department of Immunology, Erasmus Medical Center Rotterdam</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>17 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Ritgen, Matthias" sort="Ritgen, Matthias" uniqKey="Ritgen M" first="Matthias" last="Ritgen">Matthias Ritgen</name><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Medical Department II, University of Schleswig-Holstein, City Hospital Kiel</s1><s2>Kiel</s2><s3>DEU</s3><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="2">Schleswig-Holstein</region><settlement type="city">Kiel</settlement></placeName></affiliation></author><author><name sortKey="Kneba, Michael" sort="Kneba, Michael" uniqKey="Kneba M" first="Michael" last="Kneba">Michael Kneba</name><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Medical Department II, University of Schleswig-Holstein, City Hospital Kiel</s1><s2>Kiel</s2><s3>DEU</s3><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="2">Schleswig-Holstein</region><settlement type="city">Kiel</settlement></placeName></affiliation></author><author><name sortKey="Asikanius, Elina" sort="Asikanius, Elina" uniqKey="Asikanius E" first="Elina" last="Asikanius">Elina Asikanius</name><affiliation wicri:level="1"><inist:fA14 i1="15"><s1>F. Hoffmann-La Roche</s1><s2>Basel</s2><s3>CHE</s3><sZ>20 aut.</sZ></inist:fA14><country>Suisse</country><wicri:noRegion>F. Hoffmann-La Roche</wicri:noRegion></affiliation></author><author><name sortKey="Humphrey, Kathryn" sort="Humphrey, Kathryn" uniqKey="Humphrey K" first="Kathryn" last="Humphrey">Kathryn Humphrey</name><affiliation wicri:level="1"><inist:fA14 i1="16"><s1>F. Hoffmann-La Roche</s1><s2>Welwyn</s2><s3>GBR</s3><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>F. Hoffmann-La Roche</wicri:noRegion></affiliation></author><author><name sortKey="Wenger, Michael" sort="Wenger, Michael" uniqKey="Wenger M" first="Michael" last="Wenger">Michael Wenger</name><affiliation wicri:level="1"><inist:fA14 i1="17"><s1>Genentech</s1><s2>South San Francisco, CA</s2><s3>USA</s3><sZ>22 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Genentech</wicri:noRegion></affiliation></author><author><name sortKey="Hallek, Michael" sort="Hallek, Michael" uniqKey="Hallek M" first="Michael" last="Hallek">Michael Hallek</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>German CLL Study Group, Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne</s1><s2>Cologne</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>14 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>University Hospital Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Cluster of Excellence "Cellular Stress Responses in Aging-Associated Diseases" (CECAD), University of Cologne</s1><s2>Cologne</s2><s3>DEU</s3><sZ>23 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>University of Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">14-0064653</idno><date when="2014">2014</date><idno type="stanalyst">PASCAL 14-0064653 INIST</idno><idno type="RBID">Pascal:14-0064653</idno><idno type="wicri:Area/PascalFrancis/Corpus">000528</idno><idno type="wicri:Area/PascalFrancis/Curation">005930</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000175</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000175</idno><idno type="wicri:doubleKey">0028-4793:2014:Goede V:obinutuzumab:plus:chlorambucil</idno><idno type="wicri:Area/Main/Merge">004099</idno><idno type="wicri:Area/Main/Curation">004039</idno><idno type="wicri:Area/Main/Exploration">004039</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions</title><author><name sortKey="Goede, Valentin" sort="Goede, Valentin" uniqKey="Goede V" first="Valentin" last="Goede">Valentin Goede</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>German CLL Study Group, Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne</s1><s2>Cologne</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>14 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>University Hospital Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department for Geriatric Medicine and Research, St. Marien Hospital and University of Cologne</s1><s2>Cologne</s2><s3>DEU</s3><sZ>1 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>St. Marien Hospital and University of Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation></author><author><name sortKey="Fischer, Kirsten" sort="Fischer, Kirsten" uniqKey="Fischer K" first="Kirsten" last="Fischer">Kirsten Fischer</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>German CLL Study Group, Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne</s1><s2>Cologne</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>14 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>University Hospital Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation></author><author><name sortKey="Busch, Raymonde" sort="Busch, Raymonde" uniqKey="Busch R" first="Raymonde" last="Busch">Raymonde Busch</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Institute of Medical Statistics and Epidemiology, Technical University Munich</s1><s2>Munich</s2><s3>DEU</s3><sZ>3 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName></affiliation></author><author><name sortKey="Engelke, Anja" sort="Engelke, Anja" uniqKey="Engelke A" first="Anja" last="Engelke">Anja Engelke</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>German CLL Study Group, Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne</s1><s2>Cologne</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>14 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>University Hospital Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation></author><author><name sortKey="Eichhorst, Barbara" sort="Eichhorst, Barbara" uniqKey="Eichhorst B" first="Barbara" last="Eichhorst">Barbara Eichhorst</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>German CLL Study Group, Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne</s1><s2>Cologne</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>14 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>University Hospital Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation></author><author><name sortKey="Wendtner, Clemens M" sort="Wendtner, Clemens M" uniqKey="Wendtner C" first="Clemens M." last="Wendtner">Clemens M. Wendtner</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>German CLL Study Group, Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne</s1><s2>Cologne</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>14 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>University Hospital Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Klinikum Schwabing</s1><s2>Munich</s2><s3>DEU</s3><sZ>6 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName></affiliation></author><author><name sortKey="Chagorova, Tatiana" sort="Chagorova, Tatiana" uniqKey="Chagorova T" first="Tatiana" last="Chagorova">Tatiana Chagorova</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Penza Regional Oncology Dispensary</s1><s2>Penza</s2><s3>RUS</s3><sZ>7 aut.</sZ></inist:fA14><country>Russie</country><wicri:noRegion>Penza Regional Oncology Dispensary</wicri:noRegion></affiliation></author><author><name sortKey="De La Serna, Javier" sort="De La Serna, Javier" uniqKey="De La Serna J" first="Javier" last="De La Serna">Javier De La Serna</name><affiliation wicri:level="3"><inist:fA14 i1="10"><s1>Servicio De Hematologia, Hospital Universitario 12 De Octubre</s1><s2>Madrid</s2><s3>ESP</s3><sZ>8 aut.</sZ></inist:fA14><country>Espagne</country><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName></affiliation></author><author><name sortKey="Dilhuydy, Marie Sarah" sort="Dilhuydy, Marie Sarah" uniqKey="Dilhuydy M" first="Marie-Sarah" last="Dilhuydy">Marie-Sarah Dilhuydy</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Hôpital Haut Lévêque</s1><s2>Bordeaux, Pessac</s2><s3>FRA</s3><sZ>9 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>Pessac</wicri:noRegion><wicri:noRegion>Hôpital Haut Lévêque</wicri:noRegion><wicri:noRegion>Hôpital Haut Lévêque</wicri:noRegion></affiliation></author><author><name sortKey="Illmer, Thomas" sort="Illmer, Thomas" uniqKey="Illmer T" first="Thomas" last="Illmer">Thomas Illmer</name></author><author><name sortKey="Opat, Stephen" sort="Opat, Stephen" uniqKey="Opat S" first="Stephen" last="Opat">Stephen Opat</name><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Department of Haematology, Monash Medical Centre</s1><s2>Clayton</s2><s3>AUS</s3><sZ>11 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Clayton</wicri:noRegion></affiliation></author><author><name sortKey="Owen, Carolyn J" sort="Owen, Carolyn J" uniqKey="Owen C" first="Carolyn J." last="Owen">Carolyn J. Owen</name><affiliation wicri:level="4"><inist:fA14 i1="13"><s1>University of Calgary</s1><s2>Calgary, AB</s2><s3>CAN</s3><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Calgary</settlement><region type="state">Alberta</region></placeName><orgName type="university">Université de Calgary</orgName></affiliation></author><author><name sortKey="Samoylova, Olga" sort="Samoylova, Olga" uniqKey="Samoylova O" first="Olga" last="Samoylova">Olga Samoylova</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Regional Clinical Hospital N.A. Semashko</s1><s2>Nizhny Novgorod</s2><s3>RUS</s3><sZ>13 aut.</sZ></inist:fA14><country>Russie</country><wicri:noRegion>Regional Clinical Hospital N.A. Semashko</wicri:noRegion></affiliation></author><author><name sortKey="Kreuzer, Karl Anton" sort="Kreuzer, Karl Anton" uniqKey="Kreuzer K" first="Karl-Anton" last="Kreuzer">Karl-Anton Kreuzer</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>German CLL Study Group, Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne</s1><s2>Cologne</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>14 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>University Hospital Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation></author><author><name sortKey="Stilgenbauer, Stephan" sort="Stilgenbauer, Stephan" uniqKey="Stilgenbauer S" first="Stephan" last="Stilgenbauer">Stephan Stilgenbauer</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Department of Internal Medicine III, Ulm University</s1><s2>Ulm</s2><s3>DEU</s3><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Ulm</settlement></placeName></affiliation></author><author><name sortKey="Dohner, Hartmut" sort="Dohner, Hartmut" uniqKey="Dohner H" first="Hartmut" last="Döhner">Hartmut Döhner</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Department of Internal Medicine III, Ulm University</s1><s2>Ulm</s2><s3>DEU</s3><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Ulm</settlement></placeName></affiliation></author><author><name sortKey="Langerak, Anton W" sort="Langerak, Anton W" uniqKey="Langerak A" first="Anton W." last="Langerak">Anton W. Langerak</name><affiliation wicri:level="3"><inist:fA14 i1="14"><s1>Department of Immunology, Erasmus Medical Center Rotterdam</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>17 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Ritgen, Matthias" sort="Ritgen, Matthias" uniqKey="Ritgen M" first="Matthias" last="Ritgen">Matthias Ritgen</name><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Medical Department II, University of Schleswig-Holstein, City Hospital Kiel</s1><s2>Kiel</s2><s3>DEU</s3><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="2">Schleswig-Holstein</region><settlement type="city">Kiel</settlement></placeName></affiliation></author><author><name sortKey="Kneba, Michael" sort="Kneba, Michael" uniqKey="Kneba M" first="Michael" last="Kneba">Michael Kneba</name><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Medical Department II, University of Schleswig-Holstein, City Hospital Kiel</s1><s2>Kiel</s2><s3>DEU</s3><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="2">Schleswig-Holstein</region><settlement type="city">Kiel</settlement></placeName></affiliation></author><author><name sortKey="Asikanius, Elina" sort="Asikanius, Elina" uniqKey="Asikanius E" first="Elina" last="Asikanius">Elina Asikanius</name><affiliation wicri:level="1"><inist:fA14 i1="15"><s1>F. Hoffmann-La Roche</s1><s2>Basel</s2><s3>CHE</s3><sZ>20 aut.</sZ></inist:fA14><country>Suisse</country><wicri:noRegion>F. Hoffmann-La Roche</wicri:noRegion></affiliation></author><author><name sortKey="Humphrey, Kathryn" sort="Humphrey, Kathryn" uniqKey="Humphrey K" first="Kathryn" last="Humphrey">Kathryn Humphrey</name><affiliation wicri:level="1"><inist:fA14 i1="16"><s1>F. Hoffmann-La Roche</s1><s2>Welwyn</s2><s3>GBR</s3><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>F. Hoffmann-La Roche</wicri:noRegion></affiliation></author><author><name sortKey="Wenger, Michael" sort="Wenger, Michael" uniqKey="Wenger M" first="Michael" last="Wenger">Michael Wenger</name><affiliation wicri:level="1"><inist:fA14 i1="17"><s1>Genentech</s1><s2>South San Francisco, CA</s2><s3>USA</s3><sZ>22 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Genentech</wicri:noRegion></affiliation></author><author><name sortKey="Hallek, Michael" sort="Hallek, Michael" uniqKey="Hallek M" first="Michael" last="Hallek">Michael Hallek</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>German CLL Study Group, Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne</s1><s2>Cologne</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>14 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>University Hospital Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Cluster of Excellence "Cellular Stress Responses in Aging-Associated Diseases" (CECAD), University of Cologne</s1><s2>Cologne</s2><s3>DEU</s3><sZ>23 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>University of Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">The New England journal of medicine</title><title level="j" type="abbreviated">N. Engl. j. med.</title><idno type="ISSN">0028-4793</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">The New England journal of medicine</title><title level="j" type="abbreviated">N. Engl. j. med.</title><idno type="ISSN">0028-4793</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antineoplastic agent</term><term>Chlorambucil</term><term>Drug combination</term><term>Human</term><term>Medicine</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Chlorambucil</term><term>Association médicamenteuse</term><term>Médecine</term><term>Homme</term><term>Anticancéreux</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Médecine</term><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">BACKGROUND The monoclonal anti-CD20 antibody rituximab, combined with chemotherapeutic agents, has been shown to prolong overall survival in physically fit patients with previously untreated chronic lymphocytic leukemia (CLL) but not in those with coexisting conditions. We investigated the benefit of the type 2, glycoengineered antibody obinutuzumab (also known as GA101) as compared with that of rituximab, each combined with chlorambucil, in patients with previously untreated CLL and coexisting conditions. METHODS We randomly assigned 781 patients with previously untreated CLL and a score higher than 6 on the Cumulative Illness Rating Scale (CIRS) (range, 0 to 56, with higher scores indicating worse health status) or an estimated creatinine clearance of 30 to 69 ml per minute to receive chlorambucil, obinutuzumab plus chlorambucil, or rituximab plus chlorambucil. The primary end point was investigator-assessed progression-free survival. RESULTS The patients had a median age of 73 years, creatinine clearance of 62 ml per minute, and CIRS score of 8 at baseline. Treatment with obinutuzumab-chlorambucil or rituximab-chlorambucil, as compared with chlorambucil monotherapy, increased response rates and prolonged progression-free survival (median progression-free survival, 26.7 months with obinutuzumab-chlorambucil vs. 11.1 months with chlorambucil alone; hazard ratio for progression or death, 0.18; 95% confidence interval [CI], 0.13 to 0.24; P<0.001; and 16.3 months with rituximab-chlorambucil vs. 11.1 months with chlorambucil alone; hazard ratio, 0.44; 95% CI, 0.34 to 0.57; P<0.001). Treatment with obinutuzumab-chlorambucil, as compared with chlorambucil alone, prolonged overall survival (hazard ratio for death, 0.41; 95% CI, 0.23 to 0.74; P=0.002). Treatment with obinutuzumab-chlorambucil, as compared with rituximab-chlorambucil, resulted in prolongation of progression-free survival (hazard ratio, 0.39; 95% CI, 0.31 to 0.49; P<0.001) and higher rates of complete response (20.7% vs. 7.0%) and molecular response. Infusion-related reactions and neutropenia were more common with obinutuzumab-chlorambucil than with rituximab-chlorambucil, but the risk of infection was not increased. CONCLUSIONS Combining an anti-CD20 antibody with chemotherapy improved outcomes in patients with CLL and coexisting conditions. In this patient population, obinutuzumab was superior to rituximab when each was combined with chlorambucil.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Canada</li><li>Espagne</li><li>France</li><li>Pays-Bas</li><li>Royaume-Uni</li><li>Russie</li><li>Suisse</li><li>États-Unis</li></country><region><li>Alberta</li><li>Bade-Wurtemberg</li><li>Bavière</li><li>Communauté de Madrid</li><li>District de Haute-Bavière</li><li>District de Tübingen</li><li>Hollande-Méridionale</li><li>Schleswig-Holstein</li></region><settlement><li>Calgary</li><li>Kiel</li><li>Madrid</li><li>Munich</li><li>Rotterdam</li><li>Ulm</li></settlement><orgName><li>Université de Calgary</li></orgName></list><tree><noCountry><name sortKey="Illmer, Thomas" sort="Illmer, Thomas" uniqKey="Illmer T" first="Thomas" last="Illmer">Thomas Illmer</name></noCountry><country name="Allemagne"><noRegion><name sortKey="Goede, Valentin" sort="Goede, Valentin" uniqKey="Goede V" first="Valentin" last="Goede">Valentin Goede</name></noRegion><name sortKey="Busch, Raymonde" sort="Busch, Raymonde" uniqKey="Busch R" first="Raymonde" last="Busch">Raymonde Busch</name><name sortKey="Dohner, Hartmut" sort="Dohner, Hartmut" uniqKey="Dohner H" first="Hartmut" last="Döhner">Hartmut Döhner</name><name sortKey="Eichhorst, Barbara" sort="Eichhorst, Barbara" uniqKey="Eichhorst B" first="Barbara" last="Eichhorst">Barbara Eichhorst</name><name sortKey="Engelke, Anja" sort="Engelke, Anja" uniqKey="Engelke A" first="Anja" last="Engelke">Anja Engelke</name><name sortKey="Fischer, Kirsten" sort="Fischer, Kirsten" uniqKey="Fischer K" first="Kirsten" last="Fischer">Kirsten Fischer</name><name sortKey="Goede, Valentin" sort="Goede, Valentin" uniqKey="Goede V" first="Valentin" last="Goede">Valentin Goede</name><name sortKey="Hallek, Michael" sort="Hallek, Michael" uniqKey="Hallek M" first="Michael" last="Hallek">Michael Hallek</name><name sortKey="Hallek, Michael" sort="Hallek, Michael" uniqKey="Hallek M" first="Michael" last="Hallek">Michael Hallek</name><name sortKey="Kneba, Michael" sort="Kneba, Michael" uniqKey="Kneba M" first="Michael" last="Kneba">Michael Kneba</name><name sortKey="Kreuzer, Karl Anton" sort="Kreuzer, Karl Anton" uniqKey="Kreuzer K" first="Karl-Anton" last="Kreuzer">Karl-Anton Kreuzer</name><name sortKey="Ritgen, Matthias" sort="Ritgen, Matthias" uniqKey="Ritgen M" first="Matthias" last="Ritgen">Matthias Ritgen</name><name sortKey="Stilgenbauer, Stephan" sort="Stilgenbauer, Stephan" uniqKey="Stilgenbauer S" first="Stephan" last="Stilgenbauer">Stephan Stilgenbauer</name><name sortKey="Wendtner, Clemens M" sort="Wendtner, Clemens M" uniqKey="Wendtner C" first="Clemens M." last="Wendtner">Clemens M. Wendtner</name><name sortKey="Wendtner, Clemens M" sort="Wendtner, Clemens M" uniqKey="Wendtner C" first="Clemens M." last="Wendtner">Clemens M. Wendtner</name></country><country name="Russie"><noRegion><name sortKey="Chagorova, Tatiana" sort="Chagorova, Tatiana" uniqKey="Chagorova T" first="Tatiana" last="Chagorova">Tatiana Chagorova</name></noRegion><name sortKey="Samoylova, Olga" sort="Samoylova, Olga" uniqKey="Samoylova O" first="Olga" last="Samoylova">Olga Samoylova</name></country><country name="Espagne"><region name="Communauté de Madrid"><name sortKey="De La Serna, Javier" sort="De La Serna, Javier" uniqKey="De La Serna J" first="Javier" last="De La Serna">Javier De La Serna</name></region></country><country name="France"><noRegion><name sortKey="Dilhuydy, Marie Sarah" sort="Dilhuydy, Marie Sarah" uniqKey="Dilhuydy M" first="Marie-Sarah" last="Dilhuydy">Marie-Sarah Dilhuydy</name></noRegion></country><country name="Australie"><noRegion><name sortKey="Opat, Stephen" sort="Opat, Stephen" uniqKey="Opat S" first="Stephen" last="Opat">Stephen Opat</name></noRegion></country><country name="Canada"><region name="Alberta"><name sortKey="Owen, Carolyn J" sort="Owen, Carolyn J" uniqKey="Owen C" first="Carolyn J." last="Owen">Carolyn J. Owen</name></region></country><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="Langerak, Anton W" sort="Langerak, Anton W" uniqKey="Langerak A" first="Anton W." last="Langerak">Anton W. Langerak</name></region></country><country name="Suisse"><noRegion><name sortKey="Asikanius, Elina" sort="Asikanius, Elina" uniqKey="Asikanius E" first="Elina" last="Asikanius">Elina Asikanius</name></noRegion></country><country name="Royaume-Uni"><noRegion><name sortKey="Humphrey, Kathryn" sort="Humphrey, Kathryn" uniqKey="Humphrey K" first="Kathryn" last="Humphrey">Kathryn Humphrey</name></noRegion></country><country name="États-Unis"><noRegion><name sortKey="Wenger, Michael" sort="Wenger, Michael" uniqKey="Wenger M" first="Michael" last="Wenger">Michael Wenger</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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